Impairment of the adrenergic reserve associated with exercise intolerance in a murine model of heart failure with preserved ejection fraction

This project is funded by grants from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation—SFB 1470—A01 to FRH and PA and A02 to GGS) and from the DZHK (German Centre for Cardiovascular Research to GGS). CUO is additionally funded by the DFG (OE 688/4-1).Aim Exercise intolerance is the central symptom in patients with heart failure with preserved ejection fraction. In the present study, we investigated the adrenergic reserve both in vivo and in cardiomyocytes of a murine cardiometabolic HFpEF model. Methods 12-week-old male C57BL/6J mice were fed regular chow (control) or a high-fat diet and L-NAME (HFpEF) for 15 weeks. At 27 weeks, we performed (stress) echocardiography and exercise testing and measured the adrenergic reserve and its modulation by nitric oxide and reactive oxygen species in left ventricular cardiomyocytes. Results HFpEF mice (preserved left ventricular ejection fraction, increased E/e', pulmonary congestion [wet lung weight/TL]) exhibited reduced exercise capacity and a reduction of stroke volume and cardiac output with adrenergic stress. In ventricular cardiomyocytes isolated from HFpEF mice, sarcomere shortening had a higher amplitude and faster relaxation compared to control animals. Increased shortening was caused by a shift of myofilament calcium sensitivity. With addition of isoproterenol, there were no differences in sarcomere function between HFpEF and control mice. This resulted in a reduced inotropic and lusitropic reserve in HFpEF cardiomyocytes. Preincubation with inhibitors of nitric oxide synthases or glutathione partially restored the adrenergic reserve in cardiomyocytes in HFpEF. Conclusion In this murine HFpEF model, the cardiac output reserve on adrenergic stimulation is impaired. In ventricular cardiomyocytes, we found a congruent loss of the adrenergic inotropic and lusitropic reserve. This was caused by increased contractility and faster relaxation at rest, partially mediated by nitro-oxidative signaling.Peer reviewe

Quantitative morphological analysis of the T-tubular network of ventricular cardiomyocytes using novel image processing tools

We propose an image acquisition and processing pipeline to quantitatively characterize the morphology of the transverse tubular network of left ventricular cardiomyocytes. The approach will be an asset in quantifying the degree of structural order of this network in the context of pathophysiological modifications

Monads for (n)omads

Από την πρώτη στιγμή της εμφάνισης της ζωής στη γη, η κινητικότητα αποτέλεσε φαινόμενο άμεσα συνδεδεμένο με αυτή. Ο άνθρωπος στη διάρκεια των χρόνων κινείται συνεχώς για λόγους επιβίωσης, ιμπεριαλιστικούς, για λόγους εμπορίου, κλπ. Σήμερα μετακινείται, πέρα από τους παραπάνω λόγους, και προκειμένου να πραγματοποιήσει τις επαγγελματικές του υποχρεώσεις. Με αφορμή το φαινόμενο αυτό, στα πλαίσια της διπλωματικής μας, ασχοληθήκαμε με τη δημιουργία μιας ‘κοινότητας’, μιας δομής που φέρει μονάδες κατοίκησης προκειμένου να φιλοξενήσει ομάδες ανθρώπων που μπορεί να μετακινούνται για διάφορους λόγους. Η κοινότητα αποτελείται από 2 τμήματα, ένα σταθερό και ένα μεταβλητό. Το μεταβλητό αποτελεί μια μεταλλική κατασκευή που έρχεται να τοποθετηθεί όπου αυτό είναι απαραίτητο. Μπορεί να προσαρμόζεται στο εκάστωτε περιβάλλον προκειμένου να ενσωματωθεί στον τόπο της προσωρινής διαμονής. Το σταθερό αποτελούν το πλήθος των μονάδων που φέρει η μεταλλική κατασκευή, μονάδες κατοίκησης, που όμως εσωτερικά έχουν τη δυνατότητα να μεταβάλλονται προκειμένου να εξυπηρετήσουν τις ανάγκες του εκάστωτε χρήστη. Σε κάθε περίπτωση όμως, κάθε ένα από αυτά τα δύο τμήματα μπορεί να λειτουργήσει και μόνο του, είτε η μεταλλική κατασκευή σαν προέκταση του δημόσιου χώρου, πχ εκθεσιακός χώρος, είτε η κάθε μονάδα σαν ανεξάρτητη μεταφερόμενη μονάδα κατοίκησης.From the very first moment of the emergence of life on earth, mobility was a phenomenon directly connected with it. Human, over the years, was constantly moving in order to survive, for imperialist reasons, for trade, etc. Today, besides the above reasons, he keeps moving in order to carry out his professional obligations. Because of all these, in our thesis, we dealt with the creation of a 'community', a structure bearing units of habitation to accommodate groups of people that can be moving for various reasons. The community consists of 2 parts, one stable and one transformable. The transformable is a metal construction placed where necessary. It can be adapted to every environment in order to be incorporated in the site of the temporary residence. The stable is a number of units on the metal construction, units of living that have the ability to change internally to accommodate the needs of each user. In any case, both of these two parts can be handled alone either the metal construction as an extension of public space, eg in case of an exhibition, either each unit as an independent transported unit of living.Γεωργούλα Β. ΚωνσταντίναΕλένη ΑνδρέουΕυδοξία Παπαγεωργίο